chr21-46601742-T-C

Variant names:

• chr21-46601742-T-C
• rs9984765
• NM_006272.3:c.138+536A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006272.3(S100B):​c.138+536A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,100 control chromosomes in the GnomAD database, including 6,046 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (6046 hom., cov: 33)
• Consequence: S100B NM_006272.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457
• Publications: 8 publications found

Genes affected

S100B (HGNC:10500): (S100 calcium binding protein B) The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21; however, this gene is located at 21q22.3. This protein may function in Neurite extension, proliferation of melanoma cells, stimulation of Ca2+ fluxes, inhibition of PKC-mediated phosphorylation, astrocytosis and axonal proliferation, and inhibition of microtubule assembly. Chromosomal rearrangements and altered expression of this gene have been implicated in several neurological, neoplastic, and other types of diseases, including Alzheimer's disease, Down's syndrome, epilepsy, amyotrophic lateral sclerosis, melanoma, and type I diabetes. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006272.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100B	NM_006272.3	MANE Select	c.138+536A>G		intron	N/A	NP_006263.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100B	ENST00000291700.9	TSL:1 MANE Select	c.138+536A>G		intron	N/A	ENSP00000291700.4
	S100B	ENST00000367071.4	TSL:1	c.138+536A>G		intron	N/A	ENSP00000356038.4
	S100B	ENST00000397648.1	TSL:1	c.138+536A>G		intron	N/A	ENSP00000380769.1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41505 AN: 151982 Hom.: 6037 Cov.: 33

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.288

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.273 AC: 41549 AN: 152100 Hom.: 6046 Cov.: 33 AF XY: 0.270 AC XY: 20083 AN XY: 74366

African (AFR) AF: 0.362 AC: 15030 AN: 41468

American (AMR) AF: 0.213 AC: 3264 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1065 AN: 3468

East Asian (EAS) AF: 0.352 AC: 1820 AN: 5172

South Asian (SAS) AF: 0.170 AC: 821 AN: 4818

European-Finnish (FIN) AF: 0.239 AC: 2528 AN: 10584

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16093 AN: 67986

Other (OTH) AF: 0.284 AC: 599 AN: 2106

Alfa AF: 0.251 Hom.: 19097

Bravo AF: 0.277

Asia WGS AF: 0.262 AC: 909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.8
DANN	Benign	0.68
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9984765; hg19: chr21-48021655;